Renal Function Trajectories in Patients with Prior Improved eGFR Slopes and Risk of Death

Background Multiple prior studies demonstrated that patients with early Chronic Kidney Disease (CKD) and positive estimated Glomerular Filtration Rate (eGFR) slopes experience increased risk of death. We sought to characterize patients with positive eGFR slopes, examine the renal function trajectory that follows the time period where positive slope is observed, and examine the association between different trajectories and risk of death. Methods and Findings We built a cohort of 204,132 United States veterans with early CKD stage 3; eGFR slopes were defined based on Bayesian mixed-effects models using outpatient eGFR measurements between October 1999 and September 2004; to build renal function trajectories, patients were followed longitudinally thereafter (from October 2004) until September 2013. There were 41,410 (20.29%) patients with positive eGFR slope and they exhibited increased risk of death compared to patients with stable eGFR slope (HR = 1.33, CI: 1.31-1.35). There was an inverse graded association between severity of albuminuria and the odds of positive eGFR slope (OR = 0.94, CI: 0.90-0.98, and OR = 0.76, CI: 0.69-0.84 for microalbuminuria and albuminuria; respectively). Following the time period where positive eGFR slope is observed, we characterized 4 trajectory phenotypes: high eGFR intercept and positive trajectory (HIPT) (12.42%), intermediate intercept and mild negative trajectory (IIMNT) (60.04%), low intercept and fast negative trajectory (LIFNT)(23.33%), and high intercept and fast negative trajectory (HIFNT) (4.20%). Compared to IIMNT (reference group), HIPT is associated with younger age, dementia, HIV, chronic lung disease, peripheral artery disease, weight loss, and inversely associated with albuminuria; LIFNT and HIFNT were associated with diabetes, hypertension, cardiovascular disease, peripheral artery disease, and albuminuria. The risk of death at 9 years was lowest in IIMNT (HR = 1.12, CI: 1.09-1.14), highest in HIPT (HR = 1.71, CI: 1.63-1.79), and intermediate in LIFNT (HR = 1.36, CI: 1.32-1.40) and HIFNT (HR = 1.56, CI: 1.45-1.68). Conclusions Our results demonstrate that patients with positive eGFR slopes, when followed over longer period of time, follow 4 distinct trajectory phenotypes that have distinct demographic and clinical correlates and are differentially associated with risk of death.